Browse publications by year: 2016

1. Clay-starch combination for micropollutants removal from wastewater treatment plant effluent

   Mohd Amin MF, Heijman SG, Rietveld LC

   Water Sci Technol, 2016;73(7):1719-27.

   PMID: 27054745 DOI: 10.2166/wst.2016.001

   Abstract

   In this study, a new, more effective and cost-effective treatment alternative is investigated for the removal of pharmaceuticals from wastewater treatment plant effluent (WWTP-eff). The potential of combining clay with biodegradable polymeric flocculants is further highlighted. Flocculation is viewed as the best method to get the optimum outcome from clay. In addition, flocculation with cationic starch increases the biodegradability and cost of the treatment. Clay is naturally abundantly available and relatively inexpensive compared to conventional adsorbents. Experimental studies were carried out with existing naturally occurring pharmaceutical concentrations found and measured in WWTP-eff with atrazine spiking for comparison between the demineralised water and WWTP-eff matrix. Around 70% of the total measured pharmaceutical compounds were removable by the clay-starch combination. The effect of clay with and without starch addition was also highlighted.

   MeSH terms: Aluminum Silicates/chemistry*; Biodegradation, Environmental; Flocculation; Starch/chemistry*; Waste Disposal, Fluid/methods; Water Pollutants, Chemical/chemistry*; Waste Water/chemistry*; Waste Disposal Facilities
2. Fulltext Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells

   Fazalul Rahiman SS, Morgan M, Gray P, Shaw PN, Cabot PJ

   PLoS One, 2016;11(4):e0153005.

   PMID: 27055013 DOI: 10.1371/journal.pone.0153005

   Abstract

   Dynorphin 1-17, (DYN 1-17) opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP) receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) from lipopolysaccharide (LPS)-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM). Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11) on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM). These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.

   MeSH terms: Cell Nucleus/metabolism*; Dynorphins/metabolism*; Humans; Lipopolysaccharides/pharmacology*; Tumor Necrosis Factor-alpha/metabolism*; Receptors, Opioid, kappa/metabolism; Receptors, Opioid, kappa/agonists; Active Transport, Cell Nucleus/drug effects; Cell Line, Tumor; Transcription Factor RelA/metabolism*; Interleukin-1beta/metabolism*
3. Patient satisfaction and medication adherence assessment amongst patients at the diabetes medication therapy adherence clinic

   Bakar ZA, Fahrni ML, Khan TM

   Diabetes Metab Syndr, 2016 Apr-Jun;10(2 Suppl 1):S139-43.

   PMID: 27055354 DOI: 10.1016/j.dsx.2016.03.015

   Abstract

   AIMS: To determine the satisfaction and current adherence status of patients with diabetes mellitus at the diabetes Medication Therapy Adherence Clinic and the relationship between patient satisfaction and adherence.
   METHODS: This cross-sectional descriptive study was carried out at three government hospitals in the state of Johor, Malaysia. Patient's satisfaction was measured using the Patient Satisfaction with Pharmaceutical Care Questionnaire; medication adherence was measured using the eight-item Morisky Medication Adherence Scale.
   RESULTS: Of n=165 patients, 87.0% of patients were satisfied with DMTAC service (score 60-100) with mean scores of 76.8. On the basis of MMAS, 29.1% had a medium rate and 26.1% had a high rate of adherence. Females are 3.02 times more satisfied with the pharmaceutical service compared to males (OR 3.03, 95% CI 1.12-8.24, p<0.05) and non-Malays are less satisfied with pharmaceutical care provided during DMTAC compared to Malays (OR 0.32, 95% CI 0.12-0.85, p<0.05). Older patients age group ≥60 years were 3.29 times more likely to adhere to their medications (OR 3.29, 95% CI 1.10-9.86, p<0.05). Females were the most adherent compared to males (OR 2.33, 95%CI 1.10-4.93, p<0.05) and patients with secondary level of education were 2.72 times more adherent to their medications compared to those in primary school and no formal education (OR 2.72, 95%CI 1.13-6.55, p<0.05). There is a significant (p<0.01), positive fair correlation (r=0.377) between satisfaction and adherence.
   CONCLUSION: Patients were highly satisfied with DMTAC service, while their adherence levels were low. There is an association between patient satisfaction and adherence.
   Keyword: Diabetes medication therapy adherence clinic (DMTAC)
   Study site: Medication Therapy Adherence Clinic, Pharmacy, Hospitals, Johor, Malaysia

   MeSH terms: Cross-Sectional Studies; Diabetes Mellitus/drug therapy*; Diabetes Mellitus/psychology; Female; Health Services; Hospitals; Humans; Malaysia; Male; Outpatient Clinics, Hospital; Patient Compliance*; Pharmacies; Sex Factors; Logistic Models; Patient Satisfaction/ethnology*
4. Isolation of Balamuthia mandrillaris-specific antibody fragments from a bacteriophage antibody display library

   Siddiqui R, Kulsoom H, Lalani S, Khan NA

   Exp Parasitol, 2016 Jul;166:94-6.

   PMID: 27055361 DOI: 10.1016/j.exppara.2016.04.001

   Abstract

   Balamuthia mandrillaris is a protist pathogen that can cause encephalitis with a mortality rate of more than 95%. Early diagnosis followed by aggressive treatment is a pre-requisite for successful prognosis. Current methods for identifying this organism rely on culture and microscopy, antibody-based methods using animals, or involve the use of molecular tools that are expensive. Here, we describe the isolation of antibody fragments that can be used for the unequivocal identification of B. mandrillaris. B. mandrillaris-specific antibody fragments were isolated from a bacteriophage antibody display library. Individual clones were studied by enzyme-linked immunosorbent assay, and immunofluorescence. Four antibody clones showed specific binding to B. mandrillaris. The usefulness of phage antibody display technology as a diagnostic tool for isolating antibody fragments against B. mandrillaris antigens and studying their biological role(s) is discussed further.

   MeSH terms: Amebiasis/diagnosis*; Amebiasis/parasitology; Antibodies, Protozoan/isolation & purification*; Antibody Specificity; Antigens, Protozoan/immunology; Encephalitis/diagnosis*; Encephalitis/parasitology; Peptide Library*; Balamuthia mandrillaris/immunology*; Balamuthia mandrillaris/isolation & purification
5. Fulltext Novel sesquiterpene lactone analogues as potent anti-breast cancer agents

   Nakagawa-Goto K, Chen JY, Cheng YT, Lee WL, Takeya M, Saito Y, et al.

   Mol Oncol, 2016 06;10(6):921-37.

   PMID: 27055598 DOI: 10.1016/j.molonc.2016.03.002

   Abstract

   Triple-negative breast cancer (TNBC) is associated with high grade, metastatic phenotype, younger patient age, and poor prognosis. The discovery of an effective anti-TNBC agent has been a challenge in oncology. In this study, fifty-eight ester derivatives (DETDs) with a novel sesquiterpene dilactone skeleton were organically synthesized from a bioactive natural product deoxyelephantopin (DET). Among them, DETD-35 showed potent antiproliferative activities against a panel of breast cancer cell lines including TNBC cell line MDA-MB-231, without inhibiting normal mammary cells M10. DETD-35 exhibited a better effect than parental DET on inhibiting migration, invasion, and motility of MDA-MB-231 cells in a concentration-dependent manner. Comparative study of DETD-35, DET and chemotherapeutic drug paclitaxel (PTX) showed that PTX mainly caused a typical time-dependent G2/M cell-cycle arrest, while DETD-35 or DET treatment induced cell apoptosis. In vivo efficacy of DETD-35 was evaluated using a lung metastatic MDA-MB-231 xenograft mouse model. DETD-35 significantly suppressed metastatic pulmonary foci information along with the expression level of VEGF and COX-2 in SCID mice. DETD-35 also showed a synergistic antitumor effect with PTX in vitro and in vivo. This study suggests that the novel compound DETD-35 may have a potential to be further developed into a therapeutic or adjuvant agent for chemotherapy against metastatic TNBC.

   MeSH terms: Animals; Antineoplastic Agents/chemical synthesis; Antineoplastic Agents/therapeutic use*; Antineoplastic Agents/chemistry*; Breast/drug effects*; Breast/pathology; Cell Cycle/drug effects; Cell Line; Cell Movement/drug effects; Female; Lactones/chemical synthesis; Lactones/therapeutic use*; Lactones/chemistry*; Models, Molecular; Neoplasm Metastasis/pathology; Neoplasm Metastasis/prevention & control; Sesquiterpenes/chemical synthesis; Sesquiterpenes/therapeutic use*; Sesquiterpenes/chemistry*; Mice, SCID; Apoptosis/drug effects; Crystallography, X-Ray; Cell Line, Tumor; Mice; Triple Negative Breast Neoplasms/drug therapy*; Triple Negative Breast Neoplasms/pathology
6. Non-thermal plasma for air and water remediation

   Hashim SA, Samsudin FN, Wong CS, Abu Bakar K, Yap SL, Mohd Zin MF

   Arch Biochem Biophys, 2016 09 01;605:34-40.

   PMID: 27056469 DOI: 10.1016/j.abb.2016.03.032

   Abstract

   A modular typed dielectric barrier discharge (DBD) device is designed and tested for air and water remediation. The module is made of a number of DBD tubes that can be arranged in series or parallel. Each of the DBD tubes comprises inner electrode enclosed with dielectric barrier and arranged as such to provide a gap for the passage of gases. Non-thermal plasma generated in the gap effectively creates gaseous chemical reactions. Its efficacy in the remediation of gas stream containing high NOx, similar to diesel emission and wastewater containing latex, are presented. A six tubes DBD module has successfully removed more than 80% of nitric oxide from the gas stream. In another arrangement, oxygen was fed into a two tubes DBD to generate ozone for treatment of wastewater. Samples of wastewater were collected from a treatment pond of a rubber vulcanization pilot plant. The water pollution load was evaluated by the chemical oxygen demand (COD) and biological oxygen demand (BOD5) values. Preliminary results showed some improvement (about 13%) on the COD after treatment and at the same time had increased the BOD5 by 42%. This results in higher BOD5/COD ratio after ozonation which indicate better biodegradability of the wastewater.

   MeSH terms: Air*; Biodegradation, Environmental; Electricity; Nitric Oxide/chemistry; Oxygen/chemistry*; Rubber; Water/chemistry*; Water Pollutants, Chemical/analysis*; Water Purification/methods*; Biological Oxygen Demand Analysis; Plasma Gases/chemistry*; Waste Water
7. Fulltext Peperomia pellucida leaf extract as immunostimulator in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis spp. farming

   Lee SW, Sim KY, Wendy W, Zulhisyam AK

   Vet World, 2016 Mar;9(3):231-4.

   PMID: 27057104 DOI: 10.14202/vetworld.2016.231-234

   Abstract

   This study was revealed the potential of Peperomia pellucida leaf extract as an immunostimulator agent in controlling motile aeromonad septicemia due to Aeromonas hydrophila in red hybrid tilapia, Oreochromis sp.

   MeSH terms: Animals; Plant Extracts; Aeromonas hydrophila; Tilapia; Sepsis; Cichlids; Peperomia
8. Fulltext Phytochemicals and Biogenic Metallic Nanoparticles as Anticancer Agents

   Rao PV, Nallappan D, Madhavi K, Rahman S, Jun Wei L, Gan SH

   Oxid Med Cell Longev, 2016;2016:3685671.

   PMID: 27057273 DOI: 10.1155/2016/3685671

   Abstract

   Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.

   MeSH terms: Antineoplastic Agents/therapeutic use*; Antineoplastic Agents/chemistry; Humans; Neoplasms/drug therapy*; Nanomedicine; Metal Nanoparticles/therapeutic use*; Metal Nanoparticles/chemistry; Green Chemistry Technology; Phytochemicals/therapeutic use*; Phytochemicals/chemistry
9. Reliability and Validity of the Fagerstrom Test for Cigarettes Dependence among Malaysian Adolescents

   Lim KH, The CH, Lim HL, Khoo YY, Lau KJ, Yy C, et al.

   Iran J Public Health, 2016 Jan;45(1):104-5.

   PMID: 27057529
10. Fulltext The Effect of Malaria and HIV Co-Infection on Anemia: A Meta-Analysis

    Naing C, Sandhu NK, Wai VN

    Medicine (Baltimore), 2016 Apr;95(14):e3205.

    PMID: 27057848 DOI: 10.1097/MD.0000000000003205

    Abstract

    Malaria and human immunodeficiency virus (HIV) infections are globally important public health concerns. The objectives of this study were (i) to determine the prevalence of malaria and HIV co-infections in people living in endemic countries, and (ii) to assess the effect of co-infection on anemia.Studies were searched on electronic databases including PubMed, Embase, Medline, Google Scholar, and African Journals Online. Observational studies, assessing the prevalence of co-infection and reporting its association with anemia, were included. The methodological quality of included studies was assessed using a tool called the risk of bias assessment for non-randomized studies. Heterogeneity among studies was investigated with the I-square test. Pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effect model, reflected on heterogeneity among studies. Summary odds ratio (OR), summary standardized mean difference (SMD), and their corresponding 95% CIs were estimated, as appropriate. Subgroup analysis and meta-regression were performed for robustness of results. Publication bias was assessed by visualization of a funnel plot.Twenty-three studies were included in the present study. Overall, the pooled prevalence of co-infection was 19% (95% CI: 15-23%, I: 98.1%), showing 26% (95% CI: 20-32%, I: 98.7%) in adults, 12% (95% CI: 7-17%, I: 95.0) in pregnant women, and 9% (95% CI: 6-11%, I: 68.6%) in children. Anemia was comparable between the monoinfected and co-infected adults (summary OR: 1.49, 95% CI: 0.93-2.37) and increased by 49% in co-infected pregnant women (summary OR: 1.49, 95% CI: 1.14-1.94). The mean hemoglobin concentration was significantly lower in the co-infected group than the monoinfected group (summary SMD: -0.47, 95% CI: -0.61 to -0.33). The results of meta-regression on the prevalence of co-infection using the publication year and total population as covariates showed the I value remained high implying a de facto random distribution of heterogeneity. An asymmetrical funnel plot indicated the presence of publication bias. Due to heterogeneity of the studies in this review, the results have to be interpreted with caution.The findings of this study suggest that the prevalence of malaria and HIV co-infection, particularly in pregnant women, requires special attention from healthcare personnel. Better understanding of the co-infection is crucial for designing treatment strategies. Future well-powered, prospective designs assessing the interaction between malaria and HIV are recommended.

    MeSH terms: Anemia*; Humans; Malaria*; HIV Infections*
11. The clinical effectiveness of cognitive behavior therapy and an alternative medicine approach in reducing symptoms of depression in adolescents

    Charkhandeh M, Talib MA, Hunt CJ

    Psychiatry Res, 2016 05 30;239:325-30.

    PMID: 27058159 DOI: 10.1016/j.psychres.2016.03.044

    Abstract

    The main aim of the study was to investigate the effectiveness of two psychotherapeutic approaches, cognitive behavioral therapy (CBT) and a complementary medicine method Reiki, in reducing depression scores in adolescents. We recruited 188 adolescent patients who were 12-17 years old. Participants were randomly assigned to CBT, Reiki or wait-list. Depression scores were assessed before and after the 12 week interventions or wait-list. CBT showed a significantly greater decrease in Child Depression Inventory (CDI) scores across treatment than both Reiki (p

    MeSH terms: Adolescent; Complementary Therapies; Child; Depression/diagnosis; Depression/psychology; Depression/therapy*; Depressive Disorder/diagnosis; Depressive Disorder/psychology; Depressive Disorder/therapy*; Female; Humans; Iran; Male; Waiting Lists; Cognitive Therapy/methods*; Treatment Outcome; Therapeutic Touch/methods*
12. Fulltext Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism as a Risk Factor for Gestational Diabetes Mellitus: A Meta-Analysis

    Lin PC, Lin WT, Yeh YH, Wung SF

    PLoS One, 2016;11(4):e0153044.

    PMID: 27058589 DOI: 10.1371/journal.pone.0153044

    Abstract

    BACKGROUND: There are racial and ethnic differences in the prevalence of gestational diabetes mellitus (GDM). Prior meta-analyses included small samples and very limited non-Caucasian populations. Studies to determine the relationship between transcription factor 7 like-2 (TCF7L2) rs7903146 polymorphism and risk of GDM in Hispanics/Latinos are recently available. The present meta-analysis was to estimate the impact of allele variants of TCF7L2 rs7903146 polymorphism on GDM susceptibility in overall population and racial/ethnic subgroups.

    METHODS: Literature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test.

    RESULTS: A total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies.

    CONCLUSIONS: This meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.

    MeSH terms: Female; Gene Frequency; Hispanic Americans/genetics; Humans; Models, Genetic; Pregnancy; Risk Factors; Odds Ratio; Case-Control Studies; Diabetes, Gestational/genetics*; Polymorphism, Single Nucleotide; European Continental Ancestry Group/genetics; Asian Continental Ancestry Group/genetics; Transcription Factor 7-Like 2 Protein/genetics*
13. Predominance of the ST143 and ST50 Leptospira clones in the urban rat populations of Peninsular Malaysia

    Benacer D, Mohd Zain SN, Ahmed AA, Mohd Khalid MKN, Hartskeerl RA, Thong KL

    J Med Microbiol, 2016 Jun;65(6):574-577.

    PMID: 27058766 DOI: 10.1099/jmm.0.000262

    MeSH terms: Animals; Cities; Leptospira/classification*; Leptospira/genetics; Leptospirosis/microbiology; Leptospirosis/epidemiology; Leptospirosis/veterinary*; Malaysia; Rodent Diseases/microbiology*; Rodent Diseases/epidemiology; Rats; Animal Distribution
14. Fulltext A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia

    Ratanabanangkoon K, Tan KY, Eursakun S, Tan CH, Simsiriwong P, Pamornsakda T, et al.

    PLoS Negl Trop Dis, 2016 Apr;10(4):e0004565.

    PMID: 27058956 DOI: 10.1371/journal.pntd.0004565

    Abstract

    Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to only one (monospecific) or a few (polyspecific) snake venoms. This demands that each country to prepare AV against its local snake venoms, which is often not feasible. Preparation of a 'pan-specific' AV against many snakes over a wide geographical area in some countries/regions has not been possible. If a 'pan-specific' AV effective against a variety of snakes from many countries could be prepared, it could be produced economically in large volume for use in many countries and save many lives. The aim of this study was to produce a pan-specific antiserum effective against major medically important elapids in Asia. The strategy was to use toxin fractions (TFs) of the venoms in place of crude venoms in order to reduce the number of antigens the horses were exposed to. This enabled inclusion of a greater variety of elapid venoms in the immunogen mix, thus exposing the horse immune system to a diverse repertoire of toxin epitopes, and gave rise to antiserum with wide paraspecificity against elapid venoms. Twelve venom samples from six medically important elapid snakes (4 Naja spp. and 2 Bungarus spp.) were collected from 12 regions/countries in Asia. Nine of these 12 venoms were ultra-filtered to remove high molecular weight, non-toxic and highly immunogenic proteins. The remaining 3 venoms were not ultra-filtered due to limited amounts available. The 9 toxin fractions (TFs) together with the 3 crude venoms were emulsified in complete Freund's adjuvant and used to immunize 3 horses using a low dose, low volume, multisite immunization protocol. The horse antisera were assayed by ELISA and by in vivo lethality neutralization in mice. The findings were: a) The 9 TFs were shown to contain all of the venom toxins but were devoid of high MW proteins. When these TFs, together with the 3 crude venoms, were used as the immunogen, satisfactory ELISA antibody titers against homologous/heterologous venoms were obtained. b) The horse antiserum immunologically reacted with and neutralized the lethal effects of both the homologous and the 16 heterologous Asian/African elapid venoms tested. Thus, the use of TFs in place of crude venoms and the inclusion of a variety of elapid venoms in the immunogen mix resulted in antiserum with wide paraspecificity against elapid venoms from distant geographic areas. The antivenom prepared from this antiserum would be expected to be pan-specific and effective in treating envenomations by most elapids in many Asian countries. Due to economies of scale, the antivenom could be produced inexpensively and save many lives. This simple strategy and procedure could be readily adapted for the production of pan-specific antisera against elapids of other continents.
15. Fulltext Molecular cloning, sequence analysis and developmental stage expression of a putative septin gene fragment from Aedes albopictus (Diptera: Culicidae)

    Avicor SW, Wajidi MF, Jaal Z, Yahaya ZS

    Acta Biochim. Pol., 2016;63(2):243-6.

    PMID: 27059016 DOI: 10.18388/abp.2014_909

    Abstract

    Septins belong to GTPases that are involved in vital cellular activities, including cytokinesis. Although present in many organisms, they are yet to be isolated from Aedes albopictus. This study reports for the first time on a serendipitous isolation of a partial septin sequence from Ae. albopictus and its developmental expression profile. The Ae. albopictus partial septin sequence contains 591 nucleotides encoding 197 amino acids. It shares homology with several insect septin genes and has a close phylogenetic relationship with Aedes aegypti and Culex quinquefasciatus septins. The Ae. albopictus septin fragment was differentially expressed in the mosquito's developmental stages, with an increased expression in the adults.

    MeSH terms: Aedes/genetics*; Aedes/growth & development; Aedes/metabolism; Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; Phylogeny; Gene Expression; Sequence Analysis, DNA; Gene Expression Regulation, Developmental; Insect Proteins/genetics*; Insect Proteins/metabolism; Septins/genetics*; Septins/metabolism
16. Rafflesia spp.: propagation and conservation

    Wicaksono A, Mursidawati S, Sukamto LA, Teixeira da Silva JA

    Planta, 2016 Aug;244(2):289-96.

    PMID: 27059028 DOI: 10.1007/s00425-016-2512-8

    Abstract

    MAIN CONCLUSION: The propagation of Rafflesia spp. is considered to be important for future development of ornamental and other applications. Thus far, the only successful propagation technique has been grafting. This mini-review succinctly emphasizes what is known about Rafflesia species. Members of the genus Rafflesia (Rafflesiaceae), which are holoparasitic plants known to grow on a host vine, Tetrastigma sp., are widely spread from the Malayan Peninsula to various islands throughout Indonesia. The plant's geographical distribution as well as many other aspects pertaining to the basic biology of this genus have still not been studied. The young flower buds and flowers of wild Rafflesia hasseltii Suringar, Rafflesia keithii Meijer and Rafflesia cantleyi Solms-Laubach are used in local (Malaysia and Indonesia) traditional ethnomedicine as wound-healing agents, but currently no formal published research exists to validate this property. To maintain a balance between its ethnomedicinal and ornamental use, and conservation, Rafflesia spp. must be artificially cultivated to prevent overexploitation. A successful method of vegetative propagation is by host grafting using Rafflesia-impregnated Tetrastigma onto the stem of a normal Tetrastigma plant. Due to difficulties with culture contamination in vitro, callus induction was only accomplished in 2010 for the first time when picloram and 2,4-D were added to a basal Murashige and Skoog medium, and the tissue culture of holoparasitic plants continues to be extremely difficult. Seeds harvested from fertile fruit may serve as a possible method to propagate Rafflesia spp. This paper provides a brief synthesis on what is known about research related to Rafflesia spp. The objective is to further stimulate researchers to examine, through rigorous scientific discovery, the mechanisms underlying the ethnomedicinal properties, the flowering mechanisms, and suitable in vitro regeneration protocols that would allow for the fortification of germplasm conservation.

    MeSH terms: Conservation of Natural Resources*; Fruit; Phylogeny; Reproduction; Seeds; Germination; Angiosperms/growth & development*; Angiosperms/physiology; Flowers/growth & development; Tissue Culture Techniques
17. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase

    Merlot AM, Shafie NH, Yu Y, Richardson V, Jansson PJ, Sahni S, et al.

    Biochem Pharmacol, 2016 06 01;109:27-47.

    PMID: 27059255 DOI: 10.1016/j.bcp.2016.04.001

    Abstract

    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment.

    MeSH terms: Animals; Antineoplastic Agents/chemical synthesis; Antineoplastic Agents/pharmacology*; Deferoxamine/pharmacology; Endoplasmic Reticulum/drug effects; Endoplasmic Reticulum/metabolism; Endoribonucleases/genetics*; Endoribonucleases/metabolism; Heat-Shock Proteins/genetics; Heat-Shock Proteins/metabolism; Humans; Iron Chelating Agents/chemical synthesis; Iron Chelating Agents/pharmacology; Oxidation-Reduction; Phosphorylation/drug effects; Thiosemicarbazones/chemical synthesis; Thiosemicarbazones/pharmacology*; Signal Transduction; Gene Expression Regulation, Neoplastic*; Apoptosis/drug effects; Protein-Serine-Threonine Kinases/genetics*; Protein-Serine-Threonine Kinases/metabolism; Calcium-Calmodulin-Dependent Protein Kinases/genetics; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; eIF-2 Kinase/genetics*; eIF-2 Kinase/metabolism; Cell Line, Tumor; HSP40 Heat-Shock Proteins/genetics; HSP40 Heat-Shock Proteins/metabolism; Activating Transcription Factor 6/genetics*; Activating Transcription Factor 6/metabolism; Activating Transcription Factor 6/agonists; Transcription Factor CHOP/genetics; Transcription Factor CHOP/metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism; Endoplasmic Reticulum Stress/drug effects*; Endoplasmic Reticulum Stress/genetics; X-Box Binding Protein 1/genetics; X-Box Binding Protein 1/metabolism
18. Negative chromatography of hepatitis B virus-like particle: Comparative study of different adsorbent designs

    Lee MF, Chan ES, Tan WS, Tam KC, Tey BT

    J Chromatogr A, 2016 May 6;1445:1-9.

    PMID: 27059397 DOI: 10.1016/j.chroma.2016.03.066

    Abstract

    Purification of virus-like particles (VLPs) in bind-and-elute mode has reached a bottleneck. Negative chromatography has emerged as the alternative solution; however, benchmark of negative chromatography media and their respective optimized conditions are absent. Hence, this study was carried out to compare the performance of different negative chromatography media for the purification of hepatitis B VLPs (HB-VLPs) from clarified Escherichia coli feedstock. The modified anion exchange media, core-shell adsorbents (InertShell and InertLayer 1000) and polymer grafted adsorbents (SQ) were compared. The results of chromatography from packed bed column of core-shell adsorbents showed that there is a trade-off between the purity and recovery of HB-VLPs in the flowthrough fraction due to the shell thickness. Atomic force microscopic analysis revealed funnel-shaped pore channels in the shell layer which may contribute to the entrapment of HB-VLPs. A longer residence time at a lower feed flow rate (0.5ml/min) improved slightly the HB-VLPs purity in all modified adsorbents, but the recovery in InertShell reduced substantially. The preheat-treatment is not recommended for the negative chromatography as the thermal-induced co-aggregation of HCPs and HB-VLPs would flow along with HB-VLPs and thus reduced the HB-VLPs purity in the flowthrough. Further reduction in the feedstock concentration enhanced the purity of HB-VLPs especially in InertLayer 1000 but reduced substantially the recovery of HB-VLPs. In general, the polymer grafted adsorbent, SQ, performed better than the core-shell adsorbents in handling a higher feedstock concentration.

    MeSH terms: Adsorption; Anions/chemistry; Chromatography, Ion Exchange*; Hepatitis B Surface Antigens/metabolism; Hepatitis B virus/isolation & purification*; Hepatitis B virus/chemistry*; Solutions/chemistry; Virion/isolation & purification*; Virology/methods*
19. Development of novel tetra- and trinucleotide microsatellite markers for giant grouper Epinephelus lanceolatus using 454 pyrosequencing

    Kim KS, Noh CH, Moon SJ, Han SH, Bang IC

    Mol Biol Rep, 2016 Jun;43(6):541-8.

    PMID: 27059503 DOI: 10.1007/s11033-016-3980-4

    Abstract

    Giant grouper (Epinephelus lanceolatus) is a commercially important species, but its wild population has recently been classified as vulnerable. This species has significant potential for use in aquaculture, though a greater understanding of population genetics is necessary for selective breeding programs to minimize kinship for genetically healthy individuals. High-throughput pyrosequencing of genomic DNA was used to identify and characterize novel tetra- and trinucleotide microsatellite markers in giant grouper from Sabah, Malaysia. In total, of 62,763 sequences containing simple sequence repeats (SSRs) were obtained, and 78 SSR loci were selected to possibly contain tetra- and trinucleotide repeats. Of these loci, 16 had tetra- and 8 had trinucleotide repeats, all of which exhibited polymorphisms within easily genotyped regions. A total of 143 alleles were identified with an average of 5.94 alleles per locus, with mean observed and expected heterozygosities of 0.648 and 0.620, respectively. Among of them, 15 microsatellite markers were identified without null alleles and with Hardy-Weinberg equilibrium. These alleles showed a combined non-exclusion probability of 0.01138. The probability of individual identification (PID) value combined with in descending order 12 microsatellite markers was 0.00008, which strongly suggests that the use of the microsatellite markers developed in this study in various combinations would result in a high resolution method for parentage analysis and individual identification. These markers could be used to establish a broodstock management program for giant grouper and to provide a foundation for genetic studies such as population structure, parentage analysis, and kinship selection.

    MeSH terms: Alleles; Animals; Base Sequence; Gene Frequency; Perciformes/genetics*; Polymorphism, Genetic; Linkage Disequilibrium; Microsatellite Repeats; Genetic Loci; Multilocus Sequence Typing; High-Throughput Nucleotide Sequencing
20. The genetic history of Peninsular Malaysia

    Norhalifah HK, Syaza FH, Chambers GK, Edinur HA

    Gene, 2016 Jul 15;586(1):129-35.

    PMID: 27060406 DOI: 10.1016/j.gene.2016.04.008

    Abstract

    This article explores the genetic history of the various sub-populations currently living in Peninsular Malaysia. This region has received multiple waves of migrants like the Orang Asli in prehistoric times and the Chinese, Indians, Europeans and Arabs during historic times. There are three highly distinct lineages that make up the Orang Asli; Semang, Senoi and Proto-Malays. The Semang, who have 'Negrito' characteristics, represent the first human settlers in Peninsular Malaysia arriving from about 50,000ya. The Senoi later migrated from Indochina and are a mix between an Asian Neolithic population and the Semang. These Asian genomes probably came in before Austroasiatic languages arrived between 5000 and 4000years ago. Semang and Senoi both now speak Austro-Asiatic languages indicative of cultural diffusion from Senoi to Semang. In contrast, the Proto-Malays who came last to the southern part of this region speak Austronesian language and are Austronesians with some Negrito admixture. It is from this group that the contemporary Malays emerged. Here we provide an overview of the best available genetic evidences (single nucleotide polymorphisms, mitochondrial DNA, Y-chromosome, blood groups, human platelet antigen, human leukocyte antigen, human neutrophil antigen and killer-cell immunoglobulin-like receptor) supporting the complex genetic history of Peninsular Malaysia. Large scale sampling and high throughput genetic screening programmes such as those using genome-wide single nucleotide polymorphism analyses have provided insights into various ancestral and admixture genetic fractions in this region. Given the now extensive admixture present in the contemporary descendants of ancient sub-populations in Peninsular Malaysia, improved reconstruction of human migration history in this region will require new evidence from ancient DNA in well-preserved skeletons. All other aspects of the highly diverse and complex genetic makeup in Peninsular Malaysia should be considered carefully for genetic mapping of disease loci and policy formation by health authorities.

    MeSH terms: Blood Group Antigens; Chromosomes; DNA, Mitochondrial; Genetic Testing; HLA Antigens; Humans; Immunoglobulins; Language; Malaysia; Neutrophils; Transients and Migrants; Antigens, Human Platelet; Arabs; Polymorphism, Single Nucleotide; Asian Continental Ancestry Group; Receptors, KIR; Human Migration; DNA, Ancient